Right Ventricular Hemodynamics Research Articles

0164: Validation of two-dimensional speckle tracking strain for assessment of early right ventricular dysfunction: in vivo and ex vivo study

Right ventricular (RV) dysfunction is a major determinant of long-term survival in congenital heart diseases. Early echo detection of RV failure is mandatory, but recent indices need to be validated. Objectives were to: (1) validate standard and strain echo indices for evaluation of RV systolic function, compared to hemodynamic parameters; (2) assess the accuracy of these indices for early detection of RV failure. Combined RV overload as observed in repaired tetralogy of Fallot was surgically reproduced in 2-month-old piglets (n=6). Age-matched piglets were used as controls (n=4). RV function was evaluated at baseline and 4 months of follow-up by standard and strain echo indices, compared to conductance catheter. Sarcomere shortening and calcium transients were recorded in RV isolated myocytes (IonOptix). Contractile reserve was assessed by in-vivo (dobutamine 5µg/kg) and ex-vivo (isoprenaline 100nM) β adrenergic stimulation. The integrity of T-tubules was controlled after Di-4-Anepps labeling. 4 months after surgery, hemodynamic RV ejection fraction (FEVD) was significantly decreased (29.7% [26.2-34] vs 42.9% [40.7-48.6], p<0.01), and inotropic responses to dobutamine were blunted (contractile reserve ΔEmax=51% vs 193%, p<0.05). On echocardiography FAC, TAPSE, S’ peak and RV free wall longitudinal strain rate were significantly reduced and correlated with FEVD. Peaks strain rate and S’ were correlated with ΔEmax (r=0.75 and 0.78, p<0.05). Isolated RV myocytes from operated animals showed hypertrophy, decreased sarcomere shortening peak in response to isporenaline (ΔL=7.8±2.8% vs 10.7±2.9%, p<0.05), and increased spontaneous calcium waves suggesting perturbations of calcium homeostasis. In this model, both standard and strain echo indices allowed the detection of early impairments of RV function and cardiac reserve, which are associated with cardiac excitation-contraction coupling alterations.

0089 : Echocardiography and right ventricular function: validation of functional criteria compared to in-vivo and ex-vivo contractility parameters

Right ventricular (RV) dysfunction is a major determinant of long-term survival in congenital heart diseases. Early echocardiographic detection of RV failure is mandatory, but recent parameters need to be validated. Objectives were to: (1) validate standard and strain echocardiographic parameters for evaluation of RV systolic function, compared to hemodynamic parameters; (2) assess the accuracy of these parameters for early detection of RV failure. Combined RV overload as observed in repaired tetralogy of Fallot was surgically reproduced in 2-month-old piglets (n=6). Age-matched piglets were used as controls (n=4). RV function was evaluated at baseline and 4 months of follow-up by standard and strain echocardiographic parameters, compared to hemodynamic (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes (IonOptix). Contractile reserve was assessed by in-vivo (dobutamine 5奯kg) and ex-vivo (isoprenaline 100nM) ?-adrenergic stimulation. 4 months after surgery, hemodynamic RV ejection fraction (FEVD) was significantly decreased (29.7% [26.2-34] vs 42.9% [40.7-48.6], p<0.01), and inotropic responses to dobutamine were attenuated (contractile reserve ΔEmax = 51% vs 193% for controls). On echocardiography FAC, TAPSE, S’ peak and RV free wall longitudinal strain rate were significantly decreased and correlated with FEVD. Strain rate and S’ peak were correlated with ?Emax (r=0.75 and 0.78, p<0.05). Isolated RV myocytes from operated animals exhibited hypertrophy, decreased sarcomere shortening peak in response to isporenaline (ΔL= 7.8 ± 2.8% vs 10.7 ± 2.9%, p<0.05), and increased spontaneous calcium waves suggesting perturbations of calcium homeostasis. In this model, both standard and strain echocardiographic parameters allowed the detection of early impairments of RV function and cardiac reserve, which are associated with cardiac excitation-contraction coupling alterations.

Abstract 13973: Impaired Right Ventricular Hemodynamics Suggest Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome

Introduction: Metabolic syndrome (MetS) is associated with preclinical metabolic heart disease (MHD) as reflected by left ventricular (LV) diastolic dysfunction. Very little is known about right ventricular (RV) function and/or pulmonary hypertension in MetS or early MHD. Hypothesis: We tested the hypothesis that that MetS is associated with subclinical RV dysfunction and pulmonary hypertension. Methods: A total of 164 subjects with MetS but without cardiovascular disease (mean age 45 years, 71% women, mean BMI 41 kg/m 2 ), 40 similarly obese controls without MetS, and 36 non-obese healthy controls underwent echocardiography, including pulsed-wave Doppler measurement of pulmonary artery acceleration time (PAAT) and ejection time (ET). PA systolic pressure was estimated from PAAT using validated equations. Results: MetS was associated with lower tricuspid valve e', shorter PAAT, shorter ET, and larger PA diameter compared with controls (Table). A total of 24% of individuals with MetS had an abnormal PAAT (&lt;100 msec). Estimated PA systolic pressure based on PAAT was 42±10 mmHg in MetS compared with 32±10 and 32±9 mmHg in healthy and obese controls (P for ANOVA &lt;0.0001). In contrast, RV structure and systolic function were similar in MetS compared with controls ( Table ). After adjustment for age, sex, hypertension, diabetes, and body-mass index, MetS remained associated with shorter PAAT (P=0.03 vs healthy; P=0.0005 vs obese). Among MetS, PAAT was correlated with mitral mean e’ (r=0.20, P=0.004), E/A ratio (r=0.21, P=0.008), and tricuspid e’ (r=0.20, P=0.04). A total of 40% of participants with abnormal PAAT also had low mean e’ (&lt;8 cm/s). Conclusions: MetS is associated with abnormal RV hemodynamics as evidenced by shorter PAAT, which correlates with measures of LV diastolic function. Estimated PA systolic pressures are significantly higher in preclinical MetS and MHD, and raise the possibility that pulmonary hypertension contributes to the pathophysiology of MHD.

Preoperative patient optimization for mechanical circulatory support.

Two patients are presented for consideration of left ventricular assist device (LVAD) placement for mechanical circulatory support. Pertinent right heart catheterization and laboratory data are presented in Table 1. Table 1 Laboratory and hemodynamic data for patient 1 and patient 2 A 56-year-old man with ischemic cardiomyopathy with a left ventricular ejection fraction of 20%. He has had five admissions in the last six months for intravenous loop diuretics, despite dietary and medication compliance and optimization of his outpatient medical regimen. Body mass index (BMI) is 18; A 42-year-old woman presents from home with lethargy after months of “feeling sick”. On admission, blood pressure is 72/58 mmHg, heart rate is 118 beats/minutes, and oxygen saturation is 84% on room air. She is intubated and transferred to the cardiac intensive care unit, where transthoracic echocardiogram shows a dilated left ventricle with an ejection fraction of 15% and global hypokinesis of both ventricles. Both of these patients raise unique questions of how the team can best optimize their risk prior to LVAD placement in order to avoid foreseeable postoperative pitfalls. There are three common postoperative complications in LVAD patients and established pre-operative predictors and preventative strategies for each. Prior to discussing those complications, it is important to review the contraindications for LVAD placement (Table 2) (1). While these may change as technology advances, currently, the presence of any of these contraindications should obviate LVAD placement. It is also important to recognize that some contraindications are reversible and short term mechanical support can occasionally be considered in these patients. Table 2 Contraindications for permanent left ventricular assist device implantation Safeguards and pitfalls Postoperative pitfall 1: right ventricular (RV) failure In the early post-operative period, several mechanisms may contribute to RV failure, including a sudden increase in cardiac output, increased RV preload from increased venous return, and increased RV wall strain and afterload due to septal shift, and pulmonary vasoreactivity after cardiopulmonary bypass. RV failure leads to liver and renal failure, underfilling of the LV and pump causing arrhythmias or shock, and a higher peri-operative mortality (1). Table 3 lists independent clinical, laboratory, hemodynamic, and echocardiographic predictors of RV failure. Table 3 Independent predictors of RV failure after LVAD implantation Prospective data is limited regarding pre-operative interventions (aside from diligent patient selection) that effectively reduce the risk of RV failure. Anecdotal evidence and experience has suggested that pre-operative diuresis, use of intra-aortic balloon pump, and inotropic support to optimize RV preload and hemodynamics can reduce the risk of RV failure in high risk patients (1).

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension

AimsEchocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. Main methodsThirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). Key findingsPSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP≥35mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017–2.567; p=0.042] and PVR≥400dyn·s·cm−5 (OR, 1.804; 95% CI 1.131–2.877; p=0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was −20.75%, based on receiver operating characteristic curve analysis. SignificancePSS of the RV free wall might serve as a useful non-invasive indicator of PH.

Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: Determinants and impact on pump function

Right ventricular (RV) dyssynchrony has been described in pulmonary arterial hypertension (PAH), but no evidence is available on its morphologic determinants and its effect on systolic function. The aim of this study was to evaluate the morphologic determinants of RV dyssynchrony by echocardiographic and cardiac magnetic resonance imaging and its effect on systolic function. In 60 consecutive idiopathic PAH (IPAH) patients with narrow QRS, RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography, calculating the standard deviation of the times to peak systolic strain for the four mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV-SD4 (19 milliseconds) and compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Despite similar pulmonary vascular resistance and mean pulmonary arterial pressure, patients with RV-SD4 at >19 milliseconds had advanced WHO class and worse 6MWT, RV hemodynamics, RV remodeling and systolic function parameters compared with patients at ≤19 milliseconds. The morphologic determinants of RV dyssynchrony resulted RV end-diastolic area, LV diastolic eccentricity index and RV mass volume ratio (r = 0.69, r(2) = 0.47, p < 0.0001). Finally, we found a significant inverse correlation between RV mid-basal segments post-systolic shortening time and cardiac index (r = -0.64, r(2) = 0.41, p = 0.001), accounting for the significant correlation between RV-SD4 and cardiac index (r = 0.57, r(2) = 0.32, p = 0.003). In IPAH with narrow QRS, RV dyssynchrony is associated with RV dilation and eccentric hypertrophy pattern, suggesting a role of segmental wall stress heterogeneity as the major determinant of mechanical delay. Post-systolic shortening, as inefficient contraction, contributes to pump dysfunction.

Right Ventricular Outflow Tract Velocity Time Integral Is the Strongest Echo-Doppler Predictor of Right Ventricular Fibrosis in Patients with Pulmonary Arterial Hypertension

Purpose Right ventricular (RV) late gadolinium enhancement (LGE) is indicative of RV fibrosis and has correlated with pulmonary artery pressures (PAP), RV ejection fraction (RVEF) and outcomes in pulmonary hypertension patients. We evaluated whether echo-Doppler measures of RV structure, function, and hemodynamics were predictive of RV-LGE in patients with pulmonary arterial hypertension (PAH). Methods and Materials We reviewed our cardiac MRI (CMRI) and transthoracic echocardiography (TTE) databases to identify PAH patients who had TTE, CMRI and catheterization within 180 days. RV echo-Doppler quantitation was performed by a single reader blinded to patient LGE status. We compared TTE, CMRI and hemodynamic variables in RV-LGE+ and RV-LGE- groups. Results 26 PAH patients (56±16 yrs, 81% female) were included in this study. 15 (58%) had RV-LGE on CMRI. Invasive hemodynamics were similar in LGE- and LGE+ patients (mean PAP 40±21 vs. 43±12mmHg, P=0.32, RAP 11±9 vs. 7mmHg, P=0.27). RVEF (41±18% vs. 41±15%, P=0.89) and RVEDVI (103±52 vs. 101±50 ml/m2) on CMRI were also similar between groups. Echo-Doppler measures of RV geometry were similar in LGE+ and LGE- patients (RV/LV ratio 1.2±0.56 vs. 1.14±0.33, P=0.89). Echo-Doppler measures of RV function also did not predict LGE positivity (TAPSE 14±7 vs. 17±8mmHg, RVFAC 25±10% vs. 24±11%, P=0.59). Doppler hemodynamic variables were the only TTE measures that predicted LGE positivity: RV outflow tract (RVOT) velocity time integral (VTI) was higher in LGE- vs. LGE+ patients (15±5 vs. 12±2cm, P=0.02) and there were non-significant trends towards lower RVOT acceleration time (83±28 vs. 67±14ms, P=0.19) and higher estimated PAP (60±30 vs. 78±37mmHg, P=0.35) in LGE+ patients. Conclusions RVOT VTI was the strongest echo-Doppler predictor of RV fibrosis in this PAH cohort. Other standard echo-Doppler measures of RV structure and function were relatively poor in terms of predicting RV-LGE in patients with PAH.

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Efficacy of Right Ventricular Free-Wall Longitudinal Speckle-Tracking Strain for Predicting Long-Term Outcome in Patients With Pulmonary Hypertension

The development of right ventricular (RV) dysfunction in pulmonary hypertension (PH) patients is associated with adverse outcome, so that the assessment of RV function has become increasingly important in the management of such patients. The present objective was to test the hypothesis that RV free-wall longitudinal speckle-tracking strain (RV-free), an independent echocardiographic predictor of hemodynamic RV performance, can predict long-term outcome. Forty-two PH patients were studied. RV-free was calculated by averaging the 3 regional peak systolic strains for the RV free wall. For comparison, tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV index of myocardial performance, and tissue Doppler-derived tricuspid lateral annular systolic velocity were also studied. Long-term follow-up was performed for 4 years after adding PH-specific drugs. Receiver operating characteristic curve analysis identified RV-free ≤ 19.4% as the best predictor of cardiovascular events with 90% sensitivity, 69% specificity, and area under the curve of 0.819 (P=0.0001). Furthermore, the Kaplan-Meier curve indicated that patients with RV-free >19.4% experienced fewer cardiovascular events than those with RV-free ≤ 19.4% (log-rank P=0.0008). Importantly, the co-occurrence of RV-free ≤ 19.4% and TAPSE <16 mm was associated with the highest frequency of cardiovascular events. RV-free may serve as a non-invasive predictor of cardiovascular events for PH patients. Combining RV-free with TAPSE may be more effective for predicting long-term cardiovascular events.

Abstract 68: Diminazene, an Angiotensin Converting Enzyme2 (ACE2) Activator, Improves Right Heart Function in Experimental Models of Pressure Overload

BACKGROUND: Right ventricular (RV) failure due to pressure overload is a major cause of morbidity and mortality in pulmonary hypertensive patients. We and others have shown that ACE2 exerts cardiopulmonary protection against lung diseases. This has led us to hypothesize that activation of ACE2 would improve RV hemodynamics and attenuate cardiac remodeling in animal models of pressure-overload. Methods: Hypoxia and Monocrotaline (MCT) models of pressure-overload were employed to evaluate the effects of Diminazene (DIZE), an ACE2 activator. Rats were exposed to hypoxia for 28 days with simultaneous DIZE treatment (15mg/Kg). In the other model, rats were challenged with MCT (50mg/Kg).Both prevention and reversal protocols were studied in this model. In the prevention protocol, rats were co-treated with DIZE for 4-weeks, while for the reversal protocol, DIZE was injected after 3-weeks of MCT-challenge and the drug treatment continued for additional 2-weeks. Results: Hypoxia exposed rats exhibited increased ratio of right ventricular to left ventricular plus septum weights, an index of RV hypertrophy (Con:0.26+0.01; Hypoxia: 0.48+0.03), along with cardiac dysfunction in terms of higher right ventricular end diastolic pressure (RVEDP; Con:3.28+0.65; Hypoxia:9.08+0.72mmHg), elevated +dP/dt (Con:2039+230; Hypoxia:2815+156mmHg/s) and increased -dP/dt (Con:-1476+98; Hypoxia:-2663+150mmHg/s). However, DIZE improved all these cardiovascular alterations (RVH:0.38+0.01; RVEDP:7.03+0.3mmHg; +dP/dt:2086+137mmHg/s;-dP/dt: -1945+100mmHg/s). Likewise, MCT injection induced RV hypertrophy (Con:0.27+0.01; MCT:0.50+0.03) and cardiac dysfunction (RVEDP; Con:3.98+0.46; MCT: 8.54+0.56mmHg; +dP/dt; Con:2107+189; MCT:3718+222mmHg/s; -dP/dt; Con:-1545+95; MCT:-2918+238mmHg/s), which was prevented by DIZE (RVH:0.29+0.02; RVEDP:4.76+0.44mmHg; +dP/dt:2525+122mmHg/s; -dP/dt:-2076+150mmHg/s). Furthermore, MCT caused a 3-fold increase in myocardial fibrosis, which was reduced by DIZE. In the reversal protocol, DIZE attenuated RV hypertrophy and improved cardiac hemodynamics. CONCLUSIONS: Collectively, our results identify a therapeutic potential of DIZE for RV dysfunction induced by pulmonary pressure-overload.

Utility of Right Ventricular Free Wall Speckle-Tracking Strain for Evaluation of Right Ventricular Performance in Patients with Pulmonary Hypertension

The objectives of this study were to test the utility of right ventricular (RV) speckle-tracking strain as an assessment tool for RV function in patients with pulmonary hypertension (PH) compared with conventional echocardiographic parameters and to investigate the relationship of the findings obtained with RV speckle-tracking strain with the hemodynamic parameters of RV performance. Forty-five prospective consecutive patients with PH were studied. RV free wall longitudinal speckle-tracking strain (RV-free) and RV septal wall longitudinal speckle-tracking strain (RV-septal) were calculated by averaging each of three regional peak systolic strains along the entire right ventricle. The conventional echocardiographic parameters-RV fractional area change, RV myocardial performance index, tricuspid annular plane systolic excursion, and tricuspid annular peak systolic velocity-were also studied. For comparison, 22 age-matched volunteers with normal ejection fractions were studied. RV-free in patients with PH was significantly lower than that in normal controls, but RV-septal in the two groups was similar. Importantly, multivariate analysis revealed that RV-free was an independent echocardiographic predictor of hemodynamic RV performance items, including mean pulmonary artery pressure (β=-0.844, P= .001) and pulmonary vascular resistance (β= -0.045, P < .001). RV-free was also correlated with RV ejection fraction and RV end-systolic volume measured by cardiac magnetic resonance imaging and with 6-min walking distance (r= 0.60, r= 0.56, and r= 0.49, respectively, P < .05). Furthermore, the improvement in RV-free 5 ± 3 months after adding medical treatment was significantly correlated with that in 6-min walking distance (r= 0.68, P < .0001). RV-free has the potential to allow for noninvasive follow-up of patients with PH.

A role for coagulation factor Xa in experimental pulmonary arterial hypertension

Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension (PAH). However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa (FXa) inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular (RV) dysfunction and hypertrophy in the monocrotaline (MCT) model of pulmonary hypertension. Sprague-Dawley rats (n = 10 per group) were randomized to receive rivaroxaban, warfarin, enoxaparin, or placebo before receiving a subcutaneous injection of MCT 60 mg/kg or saline. Rivaroxaban and enoxaparin were administered for 28 days starting 4 h before MCT injection; warfarin was given for 35 days initiated 7 days before MCT injection. RV haemodynamics and hypertrophy were assessed 28 days after MCT administration. Rivaroxaban dose-dependently reduced systolic and end-diastolic RV pressure increase and RV hypertrophy. Warfarin reduced RV pressure increase only. Enoxaparin had no effect on either parameter. Severe bleeding occurred in four and five rats treated with warfarin and enoxaparin, respectively, whereas no overt bleeding was observed in rats treated with rivaroxaban. Selective, direct inhibition of FXa by rivaroxaban effectively prevented RV dysfunction and hypertrophy in MCT-injected rats, indicating a role for coagulation factors in experimental pulmonary hypertension. Clinical investigation of the impact of early and continued administration of a specific FXa inhibitor such as rivaroxaban on the course of PAH should be considered.

Usefulness of the Right Ventricular Systolic to Diastolic Duration Ratio to Predict Functional Capacity and Survival in Children With Pulmonary Arterial Hypertension

The objective of this study was to investigate the systolic to diastolic duration ratio (S:D ratio) in children with pulmonary arterial hypertension (PAH) and its association with right ventricular (RV) performance, hemodynamics, 6-minute walk test, clinical outcomes, and survival. We reviewed 503 serial echocardiograms in 47 children with PAH (mean pulmonary artery pressure >or=25 mm Hg) and compared the S:D ratio, assessed from Doppler flow of tricuspid valve regurgitation, to that in 47 age-matched controls. We reviewed echocardiograms, catheterization data, 6-minute walk tests, clinical data, lung transplantation, and death and used univariate linear regression models with a maximum likelihood algorithm for parameter estimation to investigate associations between S:D ratio and RV function, hemodynamics, functional capacity, and clinical outcomes. The S:D ratio was significantly higher in patients than in controls (1.38 +/- 0.61 vs 0.72 +/- 0.16, p <0.001). A higher S:D ratio was associated with worse echocardiographic RV fractional area of change, worse catheterization hemodynamics, shorter 6-minute walk distance, and worse clinical outcomes independent of pulmonary resistance or pressures. An increase of 0.1 in the S:D ratio was associated with a 13% increase in yearly risk for lung transplantation or death (hazard ratio 1.13, p <0.001). An S:D ratio 1.00 to 1.40 was associated with a moderate risk and an S:D ratio >1.40 was associated with a high risk of a negative outcome. In conclusion, in children with PAH, an increased S:D ratio is temporally associated with worse RV function, hemodynamics, exercise capability, clinical status, and survival.

Abstract 5658: Immune Reconstitution Prevents Autoimmune Inflammation and Right Ventricular Remodeling in Immunodeficiency-Associated Pulmonary Hypertension

Pulmonary arterial hypertension (PH) is a frequently lethal condition commonly associated with autoimmune conditions. Because autoimmunity is closely linked to immunodeficiency, we utilize athymic (AT) nude rats lacking normal T cells to demonstrate how PH is accentuated by a lack of normal regulatory T cell activity. The purpose of this study was to determine whether immune reconstitution (IR) prevents autoimmune inflammation (AI), right ventricular (RV) remodeling and PH using inbred AT rats reconstituted with euthymic spleen cells. Methods and Results: Inbred WAG AT nude rats were given a single injection of vascular endothelial growth factor receptor (VEGFR) antagonist SU5416 (20mg/kg sc), AT+SU group. Control AT was treated with vehicle only (DMSO). In adoptive transfer IR experiments, AT rats received unfractionated 20×10 6 euthymic rat spleen cells, CD4+T cells, CD8+T cells, CD4+CD25+T cells isolated with magnetic cell sorting before or after SU5416 administration. 2D-Echo, pulmonary hemodynamics and RV/LV+S ratio were assessed at 10d and 21d. Echo revealed decreased RV fractional shortening (p&lt;0.05) and PA acceleration time (p&lt;0.005) in AT+SU compared with IR and controls. IR prevented increase of RVSP compared to AT+SU (P&lt;0.05) and of RV/LV+S (P&lt;0.001). RV fetal cardiac gene expression (a-MHC, b-MHC, SERCA, BNP, SkACT, ANP) was consistent with pathologic stress pattern injury pattern and was significantly attenuated by IR. Furthermore, IR reduced expression of Th1, TH2 cytokines and pulmonary infiltration of macrophages, mast cells, B cells, IgG deposition and up-regulated lung BMPR2, FOXP3+, c-kit+, HOX11+ expression with increased c-kit+ and BMPR2 expression being noted in the pulmonary vascular endothelium. Conclusions: This study demonstrates that T cell deficiency is permissive for PH development and that IR prevents hemodynamic RV remodeling, attenuates AI and limits PH. Interestingly, that PH prevention is associated with increased regenerative HOX11+, C-kit stem cell populations.

Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome

To evaluate the effects of acute hypercapnia induced by positive end-expiratory pressure (PEEP) variations at constant plateau pressure (P (plat)) in patients with severe acute respiratory distress syndrome (ARDS) on right ventricular (RV) function. Prospective observational study in two academic intensive care units enrolling 11 adults with severe ARDS (PaO(2)/FiO(2) <150 mmHg at PEEP >5 cmH(2)O). We compared three ventilatory strategies, each used for 1 h, with P (plat) at 22 (20-25) cmH(2)O: low PEEP (5.4 cmH(2)O) or high PEEP (11.0 cmH(2)O) with compensation of the tidal volume reduction by either a high respiratory rate (high PEEP/high rate) or instrumental dead space decrease (high PEEP/low rate). We assessed RV function (transesophageal echocardiography), alveolar dead space (expired CO(2)), and alveolar recruitment (pressure-volume curves). Compared to low PEEP, PaO(2)/FiO(2) ratio and alveolar recruitment were increased with high PEEP. Alveolar dead space remained unchanged. Both high-PEEP strategies induced higher PaCO(2) levels [71 (60-94) and 75 (53-84), vs. 52 (43-68) mmHg] and lower pH values [7.17 (7.12-7.23) and 7.20 (7.16-7.25) vs. 7.30 (7.24-7.35)], as well as RV dilatation, LV deformation and a significant decrease in cardiac index. The decrease in stroke index tended to be negatively correlated to the increase in alveolar recruitment with high PEEP. Acidosis and hypercapnia induced by tidal volume reduction and increase in PEEP at constant P (plat) were associated with impaired RV function and hemodynamics despite positive effects on oxygenation and alveolar recruitment ( ClinicalTrials.gov #NCT00236262).

Phenotyping the Right Ventricle in Patients with Pulmonary Hypertension

Right ventricular (RV) failure is associated with poor outcomes in pulmonary hypertension (PH). We sought to phenotype the RV in PH patients with compensated and decompensated RV function by quantifying regional and global RV structural and functional changes. Twenty-two patients (age 51 +/- 11, 14 females, mean pulmonary artery (PA) pressure range 13-79 mmHg) underwent right heart catheterization, echocardiography, and ECG-gated multislice computed tomography of the chest. Patients were divided into three groups: Normal, PH with hemodynamically compensated, and decompensated RV function (PH-C and PH-D, respectively). RV wall thickness (WT) was measured at end-diastole (ED) and end-systole (ES) in three regions: infundibulum, lateral free wall, and inferior free wall. Globally, RV volumes progressively increased from Normal to PH-C to PH-D and RV ejection fraction decreased. Regionally, WT increased and fractional wall thickening (FWT) decreased in a spatially heterogeneous manner. Infundibular wall stress was elevated and FWT was lower regardless of the status of global RV function. In PH, there are significant phenotypic abnormalities in the RV even in the absence of overt hemodynamic RV decompensation. Regional changes in RV structure and function may be early markers of patients at risk for developing RV failure.

Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling

Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension. It is unclear however, whether inhibition of PDE5 can prevent myocardial remodelling during right-ventricular pressure overload. Right-ventricular pressure overload was produced in male rats in a pulmonary hypertension model (monocrotaline 60 mg/kg s.c.) or by surgical pulmonary artery banding. PDE5 inhibition using oral sildenafil (50 mg/kg/day in drinking water) or placebo was initiated 14 days after monocrotaline treatment and continued for 14 days until final examination. In the pulmonary artery banding groups, rats were treated with sildenafil (50 mg/kg/day) or placebo for 21 days following surgical pulmonary artery banding. At the final experiments, right-ventricular haemodynamics were measured and remodelling was analysed using histological, biochemical, and gene expression markers. Both monocrotaline and pulmonary artery banding increased right-ventricular systolic pressure to approximately 80 mmHg. In parallel, both interventions induced markers of hypertrophy (upregulation of natriuretic peptides, increase in myocyte diameter) and fibrosis (upregulation of collagen types 1A2 and 3A1) as well as mRNA expression of the tissue inhibitor of matrix metalloproteases 1 and osteopontin in the right ventricle. In monocrotaline model, sildenafil decreased pulmonary pressure, reduced right-ventricular hypertrophy, and prevented fibrosis marker gene upregulation. After pulmonary artery banding, in contrast, sildenafil increased markers of myocardial remodelling and right-ventricular myocyte diameter. Sildenafil prevents myocardial remodelling in pulmonary hypertension through an indirect action via right-ventricular unloading.

Isolated right ventricular dysfunction without myocardial infarction

Right ventricular (RV) infarction or dysfunction is commonly complicated with acute inferior myocardial infarction. In this report, we describe a patient with unstable angina pectoris who showed a temporary isolated RV dysfunction. The patient had total occlusion of proximal right coronary artery, including RV branch, with good collateral circulation from left coronary artery. Recanalization was obtained by percutaneous coronary intervention (PCI). Echocardiography at admission showed RV dilatation and severe hypokinesis of RV free wall but no left ventricular wall motion abnormalities. Hemodynamic examination showed high right atrial pressure with a non-compliant pattern and low cardiac output immediately after PCI. Cardiac enzymes were not elevated even after PCI. RV asynergy and hemodynamics were improved at 2 days after PCI. The 99 m technetium-pyrophosphate and 201 thallium dual single-photon emission computed tomography showed uptake of 99 m technetium-pyrophosphate in only the RV free wall, but in the left ventricle no uptake of 99 m technetium-pyrophosphate and no perfusion defect of 201 thallium.

Avoidance of Right Ventricular Pacing in Cardiac Resynchronization Therapy Improves Right Ventricular Hemodynamics in Heart Failure Patients

Cardiac resynchronization therapy (CRT) applied by pacing the left and right ventricles (BiV) has been shown to provide synchronous left ventricular (LV) contraction in heart failure patients. CRT may also be accomplished through synchronization of a properly timed LV pacing impulse with intrinsically conducted activation wave fronts. Elimination of right ventricular (RV) pacing may provide a more physiological RV contraction pattern and reduce device current drain. We evaluated the effects of LV and BiV pacing over a range of atrioventricular intervals on the performance of both ventricles. Acute LV and RV hemodynamic data from 17 patients with heart failure (EF = 30 +/- 1%) and a wide QRS (138 +/- 25 msec) or mechanical dyssynchrony were acquired during intrinsic rhythm, BiV, and LV pacing. The highest LV dP/dt(max) was achieved during LV pre- (LV paced prior to an RV sense) and BiV pacing, followed by that obtained during LV post-pacing (LV paced after an RV sense) and the lowest LV dP/dt(max) was recorded during intrinsic rhythm. Compared with BiV pacing, LV pre-pacing significantly improved RV dP/dt(max) (378 +/- 136 mmHg/second vs 397 +/- 136 mmHg/second, P < 0.05) and preserved RV cycle efficiency (61.6 +/- 14.6% vs 68.6 +/- 11.4%, P < 0.05) and stroke volume (6.6 +/- 4.4 mL vs 9.0 +/- 6.3 mL, P < 0.05). Based on LV dP/dt(max), the optimal atrioventricular interval could be estimated by subtracting 30 msec from the intrinsic atrial to sensed RV interval. Synchronized LV pacing produces acute LV and systemic hemodynamic benefits similar to BiV pacing. LV pacing at an appropriate atrioventricular interval prior to the RV sensed impulse provides superior RV hemodynamics compared with BiV pacing.

Arrhythmias in Adult Patients With Congenital Heart Disease

By the time patients with congenital heart disease (CHD) reach adolescence and early adulthood, rhythm status has often become an active issue, if not the central issue, in their cardiac management. For some, arrhythmias are intrinsic to the structural malformation itself, as is the case with Wolff-Parkinson-White syndrome in the setting of Ebstein’s anomaly, or atrioventricular (AV) block in the setting of “congenitally corrected” transposition of the great arteries (L-TGA). For most other CHD patients, arrhythmias represent an acquired condition related to the unique myocardial substrate created by surgical scars in conjunction with cyanosis and abnormal pressure/volume loads of long duration. This review will attempt to address the major rhythm difficulties faced by adults with CHD, concentrating on electrophysiological features that distinguish CHD from more conventional forms of adult heart disease. A listing of specific arrhythmias and commonly associated congenital defects is provided in Table 1 to serve as an outline for the discussion. View this table: TABLE 1. Specific Arrhythmias and Associated Defects in Adults With Congenital Heart Disease As of 2001, there were estimated to be 800 000 adults with CHD living in the United States,1 a number that has grown steadily as more survivors of childhood surgery reach maturity. Of these, roughly 45% are considered to have mild forms of CHD (eg, atrial septal defect, valvar pulmonary stenosis), 40% are classified as having moderate disease (eg, tetralogy of Fallot, Ebstein’s anomaly), and 15% are considered to have complex disease (eg, single ventricle, transposition of the great arteries). Although arrhythmias can develop within any of the 3 subgroups, the incidence is highest for patients in the moderate and severe categories. Tetralogy of Fallot is an instructive example of moderate CHD with a large arrhythmia burden. As many as one third of patients with repaired tetralogy develop symptomatic atrial tachycardias by …